It has been proposed that Oligo‐Miocene regional uplift of Madagascar was generated and is maintained by mantle dynamical processes. Expressions of regional uplift include flat‐lying Upper Cretaceous‐Paleogene marine limestones that crop out at elevations of hundreds of meters along the western seaboard and emergent Quaternary coral‐rich terraces that rim the coastline. Here, we explore the history of subcrustal topographic support through a combined analysis of four sets of observational constraints. First, we exploit published receiver function estimates of crustal thickness and spectral admittance between gravity and topography. An admittance value of ∼+40 ± 10 mGal km−1 at wavelengths >500 km implies that ∼1 km of topography is supported by subcrustal processes. Secondly, new apatite fission‐track and helium measurements from 18 basement samples are inverted, constraining temperature and denudation histories. Results suggest that 0.5–1.6 km of regional uplift occurred after ∼30 Ma. Thirdly, we calculate a history of regional uplift by minimizing the misfit between observed and calculated longitudinal river profiles. Results suggest that topography was generated during Neogene times. Finally, inverse modeling of rare earth element concentrations in Neogene mafic rocks indicates that melting of the asthenospheric source occurred at depths of ≤65 km with potential temperatures of 1300–1370 °C. Melting occurred at higher temperatures beneath Réunion Island and northern Madagascar and at lower temperatures beneath the Comores and southern Madagascar. These inferences are consistent with shear wave velocities obtained from tomographic models. We conclude that Madagascar is underlain by thinned lithospheric mantle and that a thermal anomaly lies within an asthenospheric layer beneath northern Madagascar. Key Points Oligo‐Miocene regional uplift of Madagascar appears to be generated and maintained by mantle processes Apatite fission‐track analyses suggest Neogene denudation. Rapid uplift and exhumation are consistent with fluvial drainage evolution Geochemical analysis of basalts implies elevated asthenospheric temperature beneath north of island and regionally thinned plate